二十二章抗高血压药课件

1、22章 抗高血压药Antihypertensive drugs 22章 抗高血压药Antihypertensive drugObjective掌握 氢氯噻嗪、普萘洛尔、硝苯地平、卡托普利、硝普钠的降压作用、机制、临床应用。熟悉 抗高血压药的分类，其它常用药的作用特点，抗高血压药的应用原则。了解 其它药物的降压作用特点。Objective掌握 氢氯噻嗪、普萘洛尔、硝苯地平、卡托普第二十二章抗高血压药课件第二十二章抗高血压药课件第二十二章抗高血压药课件第二十二章抗高血压药课件第二十二章抗高血压药课件第二十二章抗高血压药课件1 introduction1. Hypertension Bp140/90

2、mmHg(18.7/12kPa)The condition can be fatal if untreated, as it greatly increases the risk of thrombosis （血栓症）, stroke （卒中） and renal failure.1 introduction1. Hyperten1 introductionClassification of hypertension1 introductionClassificat1 introductionpathophysiology(病生理) of hypertension 1). sympatheti

3、c nervous system dysfunction (交感神经系统功能紊乱) SympatheticNS（）artery constriction peripheral resistance heart（）HR,CO-R(+) renin excreteBp1 introductionpathophysio2). RAAS 3). Others2). RAAS 3). Others1 introductionAntihypertensive drugs 【definition】 The agents can lower blood pressure, clinical used to t

4、reat hypertension and to prevent damages in kidney, heart and brain.【significance】 morbidity and mortality ( 发病率） （死亡率）1 introductionAntihyperte1 introductionClassification of antihypertensive drugs 1.Diuretics: DCT氢氯噻嗪, furosemide呋塞米 2. RAAS inhibitors ACEI captopril, enalapril AT1 blockers losarta

5、n氯沙坦, valsartan缬沙坦 Renin inhibitors enalkiren依那吉仑, remikiren雷米克林1 introductionClassificat1 introduction3. Adrenergic receptor blockers: 1) 1-R blockers: prazosin terazosin 2) -R blockers: propranolol 3) 、 -R blockers: labetalol4. Calcium channel blockers: nifedipine, amlodipine1 introduction3. Adren

6、erg1 introduction 5. Sympathetic nervous inhibitors: clonidine, methyldopa, reserpine. 6. Vasodilators: hydralazine , sodium nitroprusside minoxidil, diazoxide. 7. others1 introduction 5. Sympa2 usual drugs- Diuretic agents I. Diuretic agents 【antihypertensive mechanism】 early hypotensive effect diu

7、retic effect blood volume long-term effect PVR（外周血管阻力） Bp 2 usual drugs- Diureti2 usual drugs- Diuretic agents Excretion of sodium intracellular Na+ intracellular Ca2+ ； the sensitivity of blood vessel responses to NA; produce the vasodilators ( BK, PGE2). 2 usual drugs- Diureti2 usual drugs- Diuret

8、ic agents【clinical uses】噻嗪类 thiazides basic antihypertensive agents mild hypertension used alone(25mg); moderate and severe hypertension used in combination with other antihypertensive agents . （ -R blockers or ACEI )2 usual drugs- Diureti2 usual drugs- Diuretic agents 吲达帕胺 indapamide diuretic effec

9、t, direct vasodilation血管舒张Bp adverse reactions small; for patient with hyperlipidemia高脂血症: replace DCT2 usual drugs- Diureti2 usual drugs- Diuretic agents呋塞米 furosemide high efficacy diuretic, it can cause severe electrolyte imbalance （电解质失衡） only used in severe hypertension, especially with chronic

10、 renal insufficiency or cardiac failure.2 usual drugs- Diureti2 usual drugs- calcium antagonistsII、Calcium antagonists blocking calcium channel vasodilationBp nifedipine (硝苯地平) nitrendipine(尼群地平) lacidipine(拉西地平) amlodipine(氨氯地平) 2 usual drugs- calcium2 usual drugs- calcium antagonists硝苯地平 nifedipin

11、e【characteristics of action 】1. po absorption is complete ;2. It has more selectivity, used for mild or moderate hypertension. 3. used alone or in combination with diuretics and -R blockers. 2 usual drugs- calcium2 usual drugs- calcium antagonists4. Reflex sympathetic activation slight tachycardia o

12、r CO ; sustained-release preparations(缓释制剂)5. Side reaction: hypotension, rash（皮疹）, tachycardia, peripheral edema （水肿）, flushing面红and dizziness （眩晕）. 2 usual drugs- calcium2 usual drugs- calcium antagonistsClinical choice: hypertension with angina心绞痛 -nifedipine硝苯地平; with cerebral vascular disease脑血

13、管疾病 -nimoldipine尼莫地平; with tachycardia心动过速-verapamil维拉帕米 (alone or with diuretics 、-R drugs)2 usual drugs- calcium2 usual drugs- -R blocking agents III. -R blocking agents 普萘洛尔 propranolol【antihypertensive mechanism】blocks 1 R CO;blocking 1-R located in the kidney renin secretion, the activity of RA

14、AS 2 usual drugs- -R blo2 usual drugs- -R blocking agents3. blocking -R located in the CNSperipheral sympathetic activity ; （外周交感N活性）4. blocking presynaptic(突触前膜) -R2 inhibit the positive feedback（正反馈）, NA release ;5. PGI2 synthesis 血管扩张2 usual drugs- -R blo2 usual drugs- -R blocking agentspropranol

15、ol2 usual drugs- -R blo2 usual drugs- -R blocking agents【antihypertensive characteristics】mildness, slowness, long duration;2. Individual variation（个体差异） of doses; 2 usual drugs- -R blo2 usual drugs- -R blocking agents3. First line agent , most useful in antihypertensive therapy; especially with hig

16、h plasma renin activity（高肾素活性）； or with angina（心绞痛） ； or with tachycardia（心动过速）. 2 usual drugs- -R blo2 usual drugs- -R blocking agentsOther -R blocking agents 阿替洛尔 atenolol 拉贝洛尔 labetalol、 卡维洛尔 carvedilol2 usual drugs- -R blo2 usual drugs- ACEIIV. Renin-angiotensin system inhibitors ACEIcaptopril卡托

17、普利 enalapril依那普利ramipril雷米普利 benazapril贝那普利cilazapril西拉普利 fosinopril福森普利2 usual drugs- ACEIIV.2 usual drugs- ACEIBasic actions: 1. AngII的生成及作用;2. 保存BK的活性;3.保护血管内皮细胞及抗动脉粥样硬化;4.抗心肌缺血与心肌保护作用;5. 对胰岛素的敏感性;6.阻止心血管病理性重构.2 usual drugs- ACEIBas【antihypertensive mechanism】AngIAngIIBlood vessel（+）NA releaseAld

18、osteroneVSM hyperplasiaACE（kininase II）BKloss aliveproduce NO,PGI2platelet congregate聚集Vasodilator血管扩张ACEI【antihypertensive mechanism】A2 usual drugs- ACEI卡托普利 captopril【antihypertensive characteristics】1. po absorption is well ， F 70% ; 2. Vasodilatation血管扩张 PVR外周阻力 , but CO and HR are not significa

19、ntly changed ;2 usual drugs- ACEI卡托普2 usual drugs- ACEI3. cardiac protection prevention and reversion of blood vessel wall incrassation（增厚） and myocardial hypertrophy（心肌肥厚）.4. Used for all types of hypertension and severe CHF. 2 usual drugs- ACEI3. 2 usual drugs- ACEI【adverse reactions 】 1) hypotens

20、ion (3.3%); 2) characteristic cough (5%20%); 3) hyperkalaemia （高血钾）; 4) renal function*; 5) dizziness, skin rashes and alteration in taste . 2 usual drugs- ACEI【ad2 usual drugs- ACEI【contraindications】 pregnancy（妊娠） ; renovascular（肾血管） disease or to those with double aortic stenosis（双侧肾动脉狭窄）.2 usual

21、 drugs- ACEI【co(二） AT1 blockersLosartan氯沙坦Valsartan缬沙坦Candesartan坎地沙坦(二） AT1 blockersLosartan氯沙坦2 usual drugs- AT1 blockers Angiotensin II receptor（ AT1） blockers 氯沙坦 losartan competitive block AT1 PVR blood capacities Used for hypertension. side effects similar to captopril, but cough is less commo

22、n.2 usual drugs- AT1 blo3 other classical antihypertensive drugs .Acting on CNS 可乐定 clonidine 甲基多巴 methyldopa 莫索尼定 moxonidine3 other classical antihyp3 other classical antihypertensive drugs可乐定 clonidine 【characteristics of action 】 1. po absorption is well , F 71-82%； 2. the mechanism is complex: c

23、entral 2-R & I1 imidazoline-R（咪唑啉受体） (+) sympathetic activity PVR ; (+) presynaptic 2-R NA release 3 other classical antihyp3 other classical antihypertensive drugs3. Dont renal blood flow and GFR frequently use for hypertension with renal insufficiency（肾功能不全）. gastric acid secretion proper for hype

24、rtension with peptic ulcer（胃潰疡）.3 other classical antihyp3 other classical antihypertensive drugs4. used for moderate to severe hypertension ；5. untoward effects : sedation , dry mouth, orthostatic hypotension（体位性低血压）, rebound withdrawal （停药反跳）， sodium and water retention.Moxonidine莫索尼定 3 other clas

25、sical antihyp3 other classical antihypertensive drugs . Vasodilators 肼屈嗪 hydralazine the effect on arterioles veins; HR , CO , renin secretion ; alone used rarely3 other classical antihyp3 other classical antihypertensive drugshydralazinesodium nitroprusside3 other classical antihyp3 other classical

26、 antihypertensive drugs硝普钠 sodium nitroprusside【characteristics 】1. iv. gtt the effects are strong、rapid and unabiding (短暂的)；2. direct vasodilation on arterial and venous ;3 other classical antihyp3 other classical antihypertensive drugs3. used for hypertensive crisis （高血压危象）; refractory CHF（难治性心衰）;

27、 controlled hypotension . （控制性降压）3 other classical antihyp3 other classical antihypertensive drugs Ganglionic Blockers神经节阻断药 美卡拉明 mecamylamine 樟磺咪芬 trimetaphan camsilate only in treating hypertensive crisis （高血压危象）and to induce controlled hypotension（控制性降压） for neurosurgery. 3 other classical antihy

28、p3 other classical antihypertensive drugs 1 -R blockers prazosin (哌唑嗪) terazosin(特拉唑嗪) doxazosin(多沙唑嗪) 3 other classical antihyp3 other classical antihypertensive drugs哌唑嗪 prazosin 【characteristics 】1. selectively block 1-R Bp; less reflex tachycardia; prazosin3 other classical antihyp3 other classical antihypertensive drugs2. coronary artery disease冠状动脉疾病,冠心病 LDL VLDL triglyceride（甘油三酯）; HDL ;3 other classical antihyp3 other